Retrograde labeling of dorsal column postsynaptic (DCPS) neurons showed that about 1,000 of these originate from the lumbosacral enlargement. DCPS neurons and primary afferent axons are the major inputs to the dorsal column nuclei and are present in the ratio of 1:3. The descending, serotonergic input to DCPS neurons, previously posited on the basis of light-microscopic observations, has been confirmed by electron microscopy. The serotonergic axon terminals that synapse on DCPS neurons contain round or oval agranular vesicles and form symmetrical synapses. A previously unsuspected relationship between the DCPS and spinocervicothalamic systems has been detected. Antidromic stimulation of the dorsal and dorsolateral funiculi has revealed numerous neurons with branched axons ascending both funiculi. Single unit recording and intracellular HRP staining has characterized a large population of small interneurons in lamina III. These cells respond to stimulation of only some types of A-beta low-threshold mechanoreceptors. Their dendritic arbors are confirmed to lamina III and their axons synapse on targets in laminae III-IV. Immunocytochemical evidence indicates that many of these interneurons contain an enkephalin-like substance.